Cerebral oxygenation monitor during head-up and -down tilt using near-infrared spatially resolved spectroscopy

Reflectance near-infrared spectroscopy (NIRS) has become a suitable and easily manageable method to monitor cerebral oxygenation changes in presyncopal and syncopal symptoms caused by postural changing or standing. A new clinical tissue oxygenation monitor has been recently developed which measures absolute tissue haemoglobin saturation (Tissue Oxygenation Index, TOI) utilizing spatially resolved spectroscopy (SRS). The present study examined the effects of postural changes on cerebral oxygenation as reflected in SRS-NIRS findings. Cerebral oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb), and the TOI were recorded from both sides of the forehead in five healthy male subjects (age range, 28-40 years) during 90 degrees head-up tilt (HUT) and -6 degrees head-down tilt (HDT). Three series of measurements were carried out on separate days. O2Hb was decreased during HUT. TOI was significantly lower in HUT than in the supine position (SUP). There was no significant change in TOI during HDT. A significant session effect was observed in the left forehead TOI during SUP, but not in the right. SRS-NIRS measurements confirmed sub-clinical alterations of cortical oxygenation during HUT. NIRS data from the left side of the forehead, which may vary with cognitive or emotional activation, were more variable than those from the right side.     

Muscle metabolism in patients with polymyositis simultaneously evaluated by using 31P-magnetic resonance spectroscopy and near-infrared spectroscopy

Simultaneous measurements of muscle energy metabolism using (31)P-magnetic resonance spectroscopy ((31)P-MRS) and the kinetics of muscular oxygen metabolism using near-infrared spectroscopy (NIRS) were conducted in polymyositis (PM) patients. The subjects were 12 PM patients (age 45 +/- 12 years) and 12 normal controls (age 41 +/- 12 years). The muscle phosphocreatine (PCr) index and intracellular pH (pHi) were determined with (31)P-MRS and the changes in intramuscular oxygenated (oxy-Hb), deoxygenated (deoxy-Hb), and total haemoglobin (total Hb) were evaluated with NIRS . The pHi and PCr index before steroid therapy in PM patients were significantly lower during exercise than in normal controls, and their recovery was statistically significantly delayed compared with the controls. The pattern of changes in NIRS over time before steroid therapy in PM patients differed from that in normal controls. There were smaller changes in deoxy-Hb and oxy-Hb during exercise, and total Hb decreased during exercise. In contrast, the kinetics of muscular metabolism after steroid therapy showed changes similar to those seen in normal controls. Simultaneous (31)P-MRS and NIRS measurements to determine the kinetics of muscular metabolism are expected to be useful as a noninvasive approach for the evaluation of treatment effects in PM patients.     

近红外光谱技术用于运动和运动想象时大脑皮质血氧反应监测的研究

目的:使用近红外光谱技术监测运动和运动想象时大脑血氧反应的变化以探讨运动和运动想象运用于脑卒中偏瘫患者康复治疗和评价的理论依据。方法:选取64名健康大学生,随机分为两组:运动组32名,运动想象组32名。运用近红外光谱技术监测运动组受试者安静时和运动时大脑皮质的血氧代谢相应变化情况,以及运动想象组受试者安静时和运动想象时大脑皮质的血氧代谢相应变化情况,并将监测结果进行统计学比较和分析。结果:①运动时,大脑氧合血红蛋白和总血红蛋白明显增加,而还原血红蛋白下降。②运动想象时,也呈现大脑氧合血红蛋白和总血红蛋白增加,而还原血红蛋白下降。与安静时进行比较,差异均有显著性意义。结论:运动想象与实际运动同样会提高大脑皮质血氧饱和度,改善相应区域大脑皮质血氧供应。     

中央区脑膜瘤患者的功能性近红外光学成像分析及文献回顾

目的评价中央区脑膜瘤患者和对照组手指运动相关的脑激活部位之区别,探讨脑功能重组的机制。方法对1例脑膜瘤患者和2例对照进行近红外脑功能成像检查。试验采用模块设计、单手对指任务,经数据处理、统计和脑功能区定位,比较患者和对照激活区域的差别。结果对照组进行单手运动时对侧大脑半球运动区激活,脑膜瘤患者右手运动时左侧初级感觉运动皮层激活,而左手运动时右侧半球（患侧）在肿瘤后外侧初级感觉运动皮层的通道出现较弱激活,而左侧半球（健侧）初级感觉运动皮层、补充运动区、运动前区出现较强激活。结论功能性近红外脑功能成像检查可检测中央区脑肿瘤患者手部运动相关的脑功能重组。     

Cerebral oxygen saturation evaluated by near‐infrared time‐resolved spectroscopy (TRS) in pregnant women during caesarean section – a promising new method of maternal monitoring

Time‐resolved spectroscopy (TRS‐20) measures tissue oxygen saturation (%) by evaluating the absolute concentrations of oxygenated, deoxygenated and total haemoglobin based on measurement of the transit time of individual photons through a tissue of interest. We measured tissue oxygen saturation in the prefrontal lobes of the brain by TRS‐20 in eighteen pregnant women during caesarean section. In a case of placenta previa, massive bleeding immediately decreased cerebral oxygen saturation from 67·2% to 54·2%, but did not alter peripheral tissue oxygenation as measured by pulse oximetry. Four cases of pre‐eclampsia revealed chronic changes in elevated base levels of cerebral oxygen saturation, though peripheral oxygen saturation was similar to that in normotensive pregnant women. Average cerebral oxygen saturation in the cases of pre‐eclampsia before the introduction of anaesthesia was 73·6 ± 4·4 (SD)% (n = 4), significantly higher than in normotensive pregnant women, 67·2 ± 4·3% (n = 13, P<0·05). Z‐scores of cerebral oxygen saturation prior to anaesthesia positively correlated with those of systolic or diastolic blood pressure. TRS‐20 could detect acute as well as chronic changes in brain oxygen saturation in response to pregnancy‐associated complications.     

近红外光谱测量脑血氧饱和度与成人心脏骤停后接受目标体温管理患者神经系统预后的关系:系统评价和荟萃分析

目的研究脑血氧饱和度(rSO₂)在心脏骤停后综合征(PCAS)昏迷患者的目标体温管理(TTM)期间预测神经系统预后的作用。方法本研究根据PRISMA指南进行报告,检索了Pubmed、Embase、Cochane Library、Web of science、Google Scholar、Clinical gov、万方、维普、CNKI共9个数据库。除外研究类型为病例报告、综述和研究样本量小于5例的研究,收集所有在成人心脏骤停(CA)期间进行近红外光谱(NIRS)测量的研究。两名审稿人评估纳入文章的质量并提取数据。结果效应使用标准化平均差(SMD)进行标准化。结果本荟萃分析纳入11项研究,其中2项为随机对照研究,9项为观察性研究。共计681例患者。患者TTM期间NIRS测量的rSO₂值在TTM 24 h(低温结束)、TTM 24~36 h(复温阶段)和TTM 36~48 h(初始常温阶段)与神经系统预后相关(TTM 24 h:SMD=0.45,95%CI 0.29~0.61;TTM 24~36 h:SMD=1.17,95%CI 0.85~1.50;TTM 36~48 h:SMD=0.26,95%CI 0.10~0.43),良好的神经系统预后(CPC 1~2)组具有较高的rSO₂值。在TTM开始时、TTM期间和TTM 72 h的常温阶段,均未发现NIRS测量的rSO₂值与神经系统预后的相关性。结论对于行TTM的CA患者,在TTM 24~48 h期间良好神经系统预后患者NIRS测量的rSO₂值高于神经系统预后不良的患者,其中TTM 24~36 h(复温阶段)与良好神经系统预后有较强的关联。     

Effects of oxygen supplementation on cerebral oxygenation during exercise in chronic obstructive pulmonary disease patients not entitled to long-term oxygen therapy

Background: The rate of change (Δ) in cerebral oxygenation (COx) during exercise is influenced by blood flow and arterial O₂ content (CaO₂). It is currently unclear whether ΔCOx would (i) be impaired during exercise in patients with chronic obstructive pulmonary disease (COPD) who do not fulfil the current criteria for long‐term O₂ therapy but present with exercise‐induced hypoxaemia and (ii) improve with hyperoxia (FIO₂ = 0·4) in this specific sub‐population. Methods: A total of 20 non‐hypercapnic men (FEV₁ = 47·2 ± 11·5% pred) underwent incremental cycle ergometer exercise tests under normoxia and hyperoxia with ΔCOx (fold‐changes from unloaded exercise in O₂Hb) being determined by near‐infrared spectroscopy. Pulse oximetry assessed oxyhaemoglobin saturation (SpO₂), and impedance cardiography estimated changes in cardiac output (ΔQT). Results: Peak work rate and ΔCOx in normoxia were lower in eight O₂‘desaturators’ compared with 12 ‘non‐desaturators’ (P<0·05). Area under ΔCOx during sub‐maximal exercise was closely related to SpO₂ decrements in ‘desaturators’ (r = 0·92, P<0·01). These patients showed the largest improvement in peak exercise capacity with hyperoxia (P<0·05). Despite a trend to lower sub‐maximal ΔQT and mean arterial pressure with active intervention, ΔCOx was significantly improved only in this group (0·57 ± 0·20 versus 2·09 ± 0·42 for ‘non‐desaturators’ and ‘desaturators’, respectively; P<0·05). Conclusions: ΔCOx was impaired in non‐hypoxaemic patients with COPD who desaturated during exercise. Hyperoxic breathing was able to correct for these abnormalities, an effect related to enhanced CaO₂ rather than improved central haemodynamics. This indicates that O₂ supplementation ameliorates exercise COx in patients with COPD who are not currently entitled to ambulatory O₂ therapy.     

Tissue oxygenation index measured using spatially resolved spectroscopy correlates with changes in cerebral blood flow in newborn lambs

Background/Objective  Abnormal cerebral haemodynamics in very preterm infants undergoing neonatal intensive care have been associated with adverse outcome, but cerebral blood flow (CBF) is difficult to assess at the cotside. Spatially resolved spectroscopy (SRS) continuously measures cerebral tissue oxygen saturation expressed as tissue oxygenation index (TOI, %), and TOI would reflect changes in CBF with constant cerebral metabolic demand. We aimed to evaluate the relationship between simultaneous measurements of CBF (Transonic System) and TOI (Hamamatsu NIRO-200) in newborn lambs (n = 8). We hypothesised that alterations in CBF of different magnitudes and frequencies would be reflected as changes of TOI in both time domain and frequency domain analyses. Methods  A silicon cuff positioned around the common brachiocephalic artery was inflated to induce 10–30% reductions in cerebral perfusion pressure so as to produce mild-to-moderate variations of CBF. Relationships between changes in CBF and TOI were evaluated in the time domain (Pearson correlation) and frequency domain (Coherence). Results  In time domain analysis, there was significant correlation between ΔTOI (%) and ΔCBF (%) (R ² = 0.69, P < 0.001). In frequency domain analysis, CBF-TOI coherence was ≥0.5 at frequencies below 0.1 Hz, but <0.5 at higher frequencies. Conclusions  We conclude that overall TOI changes are concordant with CBF variations, when arterial oxygen saturation and cerebral oxygen consumption are constant. While TOI reflects CBF, it is more sensitive to variations of CBF of low frequency (<0.1 Hz) than to more rapid, higher frequency changes.     

Comparison of near‐infrared fluorescent deoxyglucose probes with different dyes for tumor diagnosis in vivo

Glucose plays a central role in the cellular energy metabolism. Malignant tumors exhibit an elevated rate of glycolysis over normal tissues. In this study, two near‐infrared fluorescent dyes, Cypate and ICG‐Der‐02, with different water solubility, were conjugated to 2‐amino‐2‐deoxy‐d ‐glucose (2DG) to form Cypate‐2DG and ICG‐Der‐02‐2DG, respectively, for NIR fluorescent imaging of tumors in nude mice. The clear routes and tumor targeting abilities of the two NIR fluorescent 2DG probes were compared. Results showed that ICG‐Der‐02‐2DG with higher hydrophilicity was cleared faster by kidneys than the more lipophilic Cypate‐2DG. Cypate‐2DG had slower but stronger tumor targeting ability compared with ICG‐Der‐02‐2DG. To investigate the correlation between the targeting ability of the probe and the glucose transporter (GLUT1) expression levels of cancer cells, the accumulation of Cypate‐2DG in tumors was assessed in MCF‐7/estradiol, U87MG, MCF‐7 and MDA‐MB‐435 tumor xenografts, which express different levels of GLUT1. The results show that both Cypate‐2DG and ICG‐Der‐02‐2DG possess tumor targeting ability on all the tumors examined, with a proportional correlation to GLUT1 expression. The findings demonstrate the broad applicability of these molecular probes for optical imaging of tumors and glucose‐related pathologies. Copyright © 2012 John Wiley & Sons, Ltd.     

Influence of repeated isometric contractions on muscle deoxygenation and pulmonary oxygen uptake kinetics in humans

The purpose of the present study was to compare simultaneously vastus lateralis (VL) deoxygenation and pulmonary O(2) uptake (O(2)) kinetics during fatiguing knee extension exercise with minimal cardiac load. Eight healthy subjects realized an intermittent bilateral knee-extension exercise (3-s contraction/3-s relaxation) at 40% of maximum voluntary contraction for 10 min. VL deoxygenation was recorded by near infrared spectroscopy at 2 Hz (NIRO-300, Hamamatsu Photonics, Japan) and O(2) was determined breath-by-breath (K4b(2), Cosmed, Italy). After a time delay of 16 +/- 5 s, deoxygenation kinetics at the onset of exercise followed an exponential time course at a significant faster rate than O(2) (time constant of 5.4 +/- 4.0 s vs. 31.6 +/- 10.4 s, P<0.01) reflecting a mismatch between local O(2) consumption and perfusion. Thereafter, a rise in O(2) of 223 +/- 123 ml min(-1) (consistent with the mathematical model, 259 +/- 126 ml min(-1)) was observed between minutes 2 and 10. During the same exercise time, changes in tissue oxygenation index decreased significantly and were individually correlated with the corresponding increased O(2) (P<0.05), suggesting that the majority of the slow rise of O(2) arose from the exercising limbs. Averaged heart rate increased from 67 +/- 11 to 116 +/- 20 beats min(-1) during exercise. Knee extension exercise may be relevant to estimate the cardiopulmonary and deoxygenation of working skeletal muscle responses for assessment of exercise limiting factors in clinical settings or in the exercise physiology.     

The effect of phenylephrine on arterial and venous cerebral blood flow in healthy subjects

Aim: Sympathetic regulation of the cerebral circulation remains controversial. Although intravenous phenylephrine (PE) infusion reduces the near‐infrared spectroscopy (NIRS)‐determined measure of frontal lobe oxygenation (S_cO₂) and increases middle cerebral artery mean blood velocity (MCA V_mean), suggesting α‐adrenergic‐mediated cerebral vasoconstriction, this remains unconfirmed by evaluation of arterial and venous cerebral blood flow. Methods: We determined S_cO₂, MCA V_mean, and right internal carotid artery (ICA) and internal jugular venous (IJV) blood flow (duplex ultrasound) during infusion of PE in eight supine young healthy men [26 (3) years, 177 (7) cm and 74 (8) kg; mean (SD)]. Results: Compared with saline, during infusion of PE, mean arterial pressure increased 26 ± 3% (mean ± SE) and MCA V_mean by 4·8 ± 1·9% (P<0·05), while S_cO₂ decreased by 13·7 ± 3·7% (P<0·05) with no significant changes in the arterial oxygen or carbon dioxide tensions. ICA blood flow did not change significantly in response to PE administration (351 ± 12 versus 373 ± 21 ml min^?1; P = 0·236), while IJV blood flow increased (443 ± 57 versus 507 ± 58 ml min^?1; P = 0·023). Conclusions: These findings confirm that PE induces a reduction in S_cO₂ measured by NIRS and causes an increase in MCA V_mean indicative of cerebral arterial vasoconstriction, although ICA was preserved and IJV increased. These results suggest that a decrease in S_cO₂ during infusion of PE reflects an altered cerebral contribution of arterial versus venous blood to the NIRS signal, although we cannot rule out that an effect of PE on skin blood flow is important.     

Anti‐arthritic effect of scopoletin,a coumarin compound occurring in Erycibe obtusifolia Benth stems,is associated with decreased angiogenesis in synovium

Scopoletin is the main constituent of coumarin found in the stems of Erycibe obtusifolia Benth, a traditional Chinese medicine used in the treatment of rheumatoid arthritis. We have previously demonstrated that scopoletin is able to decrease the serum level of uric acid in hyperuricemic mice induced by potassium oxonate, and attenuate croton oil‐induced inflammation. In the present study, we evaluated the anti‐arthritic effects of scopoletin in rat adjuvant‐induced arthritis by assessing paw swelling, pathology, and synovial angiogenesis. It was found that scopoletin, injected intraperitoneally at doses of 50, 100 mg/kg, reduced both inoculated and non‐inoculated paw swelling as well as articular index scores, and elevated the mean body weight of adjuvant‐induced arthritic rats. Rats treated with higher dose of scopoletin showed a near‐normal histological architecture of the joints and a reduced new blood vessel formation in the synovial tissues. Furthermore, scopoletin downregulated the overexpression of vascular endothelial growth factor, basic fibroblast growth factor and interleukin 6 in the synovial tissues of adjuvant‐induced arthritic rats. In conclusion, scopoletin is capable of ameliorating clinical symptoms of rat adjuvant‐induced arthritis, by reducing numbers of new blood vessels in the synovium and the production of important endogenous angiogenic inducers. Therefore, this compound may be a potential agent for angiogenesis‐related diseases and could serve as a structural base for screening more potent synthetic analogs.     

Fast clearing RGD‐based near‐infrared fluorescent probes for in vivo tumor diagnosis

A fast clearing hydrophilic near‐infrared (NIR) dye ICG‐Der‐02 was used to constitute tumor targeting contrast agents. Cell adhesion molecule integrin α_vβ₃ served as the target receptor because of its unique expression on almost all sprouting tumor vasculatures. The purpose of this study was to synthesize and compare the properties of integrin α_vβ₃‐targeted, fast clearing NIR probes both in vitro and in vivo for tumor diagnosis. ICG‐Der‐02 was covalently conjugated to three kinds of RGD peptide including linear, monoeric cyclic and dimeric RGD to form three RGD‐based NIR probes. The integrin receptor specificities of these probes were evaluated in vitro by confocal microscopy. The dynamic bio‐distribution and elimination ratse were in vivo real‐time monitored by a near‐infrared imaging system in normal mice. Further, the in vivo tumor targeting abilities of the RGD‐based NIR probes were compared in α_vβ₃‐positive MDA‐MB‐231, U87MG and α_vβ₃‐negtive MCF‐7 xenograft mice models. Three RGD‐based NIR probes were successfully synthesized with good optical properties. In vitro cellular experiments indicated that the probes have a clear binding affinity to α_υβ₃‐positive tumor cells, with a cyclic dimeric RGD probe owing the highest integrin affinity. Dynamic bio‐distributions of these probes showed a rapid clearing rate through the renal pathway. In vivo tumor targeting ability of the RGD‐based porbes was demonstrated on MDA‐MB‐231 and U87MG tumor models. As expected, the c(RGDyK)₂‐ICG‐Der‐02 probe displayed the highest tumor‐to‐normal tissue contrast. The in vitro and in vivo block experiments confirmed the receptor binding specificity of the probes. The hydrophilic dye‐labeled NIR probes exhibited a fast clearing rate and deep tissue penetration capability. Further, the α_υβ₃ receptor affinity of the three RGD‐based NIR probes followed the order of dimer cyclic > monomer cyclic > linear. The results demonstrate potent fast clearing probes for in vivo early tumor diagnosis. Copyright © 2012 John Wiley & Sons, Ltd.